Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset (14-86 years), dominantly inherited disorder caused by NOTCH3 mutations and is characterized by recurrent subcortical infarctions, dementia, and less frequently, migraine and psychiatric symptoms. NOTCH3 has 33 exons, and CADASIL-associated NOTCH3 mutations resulting in an uneven number of cysteine residues within a given extracellular epidermal growth factor (EGF)-like repeat (EGFL-repeat) domain with a strong clustering in exon 3 to 6 encoding the first five EGFL-repeats. The typical MRI features in CADASIL include multi-focal lacunar infarcts and diffuse T2-weighted hyperintensity of cerebral white matter with involvement of the anterior temporal lobe. Electronmicroscopy (EM) shows the presence of granular osmiophilic material (GOM) in the media of arterioles, in close vicinity to the basement membrane of the smooth muscle cells, and is pathognomonic for CADASIL.
The identity of this granular osmiophilic material is only partly known, but has been shown to contain mutated NOTCH3 protein.